Several studies suggest that gastritis, gastric ulcer and stress ulcer result from disruption of the ability of the mucosa to handle the back diffusion of H plus. Although a variety of agents have been shown to increase mucosal permeability and alter the buffering capacity of the mucosa, little is known about the mechanism(s) which allow the stomach to maintain a high transmural gradient to H plus. Recent studies suggest that the carboxyl group of salicylate is key to its damaging effects on the gastric mucosa. The relationships between the metabolic and permeability effects induced by salicylate, however, are not clear in terms of resulting ulceration. Both intraluminal and intravenous salicylate damage the gastric mucosa but the extent of damage differs depending upon the route of administration. The mechanism(s) of damage may also differ according to the route of administration. Bicarbonate secretion appears to be an important mechanism by which the mucosa protects itself against diffusing acids. There are, in addition, compounds which seem to cause mucosal retention of the "alkaline tide." This study will continue to examine the effects of salicylate and other agents on the gastric mucosa in order to further define its mechanism and sites of injury. The result will allow determination of mechanisms for maintenance and alterations of mucosal permeability. In addition to gaining insight as to the nature of the ability of the stomach to protect itself against acid, this investigation will also result in a better understanding of the complex interrelationship among ion transport processes in the stomach as well as metabolic regulation of ion transport in both fundus and antrum.